81201

APC (Adenomatous Polyposis Coli) Gene Analysis; Full Gene Sequence

CPT code 81201 describes a Tier 1 molecular pathology procedure involving the full gene sequence analysis of the Adenomatous Polyposis Coli (APC) gene. This gene is a critical tumor suppressor located on chromosome 5q21-q22. Mutations in the APC gene are the primary cause of Familial Adenomatous Polyposis (FAP), an autosomal dominant disorder characterized by the development of hundreds to thousands of adenomatous polyps in the colon and rectum. If left untreated, individuals with FAP have a nearly 100 percent risk of developing colorectal cancer, typically by age 40. This procedure involves the comprehensive sequencing of all coding exons and adjacent intronic boundaries of the APC gene to identify germline mutations, including single nucleotide variants, small insertions, and deletions. This level of testing is typically indicated when a patient presents with a clinical phenotype suggestive of FAP or Attenuated FAP (AFAP)—characterized by 10 to 100 polyps—and where a specific familial mutation has not yet been identified. The sequencing process utilizes advanced techniques such as Next-Generation Sequencing (NGS) or Sanger sequencing. The results provide definitive diagnostic information that guides clinical management, including the frequency of colonoscopic surveillance, the timing of prophylactic colectomy, and the screening protocols for extra-colonic manifestations such as desmoid tumors, osteomas, and upper gastrointestinal tract polyps. Because FAP is a hereditary condition, identifying a pathogenic variant in a proband through 81201 allows for targeted, cost-effective testing of at-risk relatives.

Clinical Indications

  • Clinical diagnosis of Familial Adenomatous Polyposis (FAP) based on >100 colorectal adenomatous polyps.
  • Clinical suspicion of Attenuated FAP (AFAP) based on 10 to 100 colorectal adenomatous polyps.
  • Presence of extra-colonic manifestations associated with APC mutations, such as desmoid tumors or hepatoblastoma.
  • Personal history of multiple colorectal adenomas occurring at an early age.
  • Absence of a known familial mutation in a patient with a strong family history of FAP or early-onset colorectal cancer.
  • Differential diagnosis from other polyposis syndromes such as MUTYH-associated polyposis (MAP) or Peutz-Jeghers syndrome.

Procedure Steps

  1. Collection of a biological specimen, typically peripheral blood in an EDTA (lavender top) tube.
  2. Isolation and purification of genomic DNA from the nucleated cells of the specimen.
  3. Assessment of DNA quality and concentration to ensure suitability for sequencing.
  4. Target enrichment or PCR amplification of all coding exons and splice-site junctions of the APC gene.
  5. DNA sequencing using Next-Generation Sequencing (NGS) platforms or automated Sanger sequencing.
  6. Bioinformatics processing of raw sequencing data to align sequences against a reference genome.
  7. Variant calling to identify deviations from the wild-type sequence.
  8. Clinical interpretation of identified variants using databases and literature (e.g., ClinVar, ACMG guidelines) to classify them as pathogenic, likely pathogenic, or variants of uncertain significance (VUS).
  9. Generation of a comprehensive molecular pathology report by a qualified laboratory director or geneticist.

Coding Guidelines

  • Report 81201 for the full sequence analysis of the APC gene.
  • If testing for only known familial variants, use CPT 81202 instead of 81201.
  • If testing specifically for duplication or deletion variants of the APC gene (e.g., using MLPA), use CPT 81203.
  • Only one APC gene analysis code should typically be reported per patient per lifetime unless medically necessary for a different indication.
  • Do not report 81201 in conjunction with multi-gene panels that already include APC (e.g., 81435) to avoid unbundling.
  • Molecular pathology Tier 1 codes should be reported for the specific gene analyzed.

Associated ICD-10 Codes